Anti-tumor activity of CPT-11 in experimental human ovarian cancer and human soft-tissue sarcoma

Willy J M Jansen, Geertruida M. Kolfschoten, Caroline A M Erkelens, Jannette Van Ark-Otte, Herbert M. Pinedo, Epie Boven

Research output: Contribution to journalArticle

Abstract

CPT-11, a semi-synthetic derivative of camptothecin, was investigated for its activity in panels of 15 human ovarian- cancer lines and 10 human soft-tissue sarcoma lines grown s.c. in nude mice. Various factors were analyzed that may be of influence on the extent of tumor-growth inhibition induced by CPT-11. At equitoxic doses, CPT-11 was more effective in the daily ×5 schedule than the weekly ×2 schedule, although a 2-fold higher dose was administered in the weekly ×2 schedule. Since i.p. and i.v. injections were similarly effective, the selected treatment schedule was 20 mg/kg i.p. daily ×5, starting when tumors measured approximately 150 mm3. Growth inhibition of ≥75% was obtained in 8/15 human ovarian-cancer lines and in 6/10 human soft-tissue sarcoma lines. A weak correlation was found between topoisomerase-1 mRNA in xenograft tissues and sensitivity to CPT-11. Relative topoisomerase-1 expression was highest in MRI-H-207 and WLS-160 xenografts, in which CPT-11 was able to induce cures of all tumors. The high efficacy in the 2 panels of human tumor lines suggests over-prediction of its potential clinical activity in these tumor types. The difference in efficacy of CPT-11 between species may be related to the metabolism of the drug, since CPT-11 is converted more efficiently into SN-38 in mice. In addition, mice may be less sensitive to SN-38-induced side-effects. On the basis of the preclinical data, frequent administration of lower doses of CPT-11 should be considered in order to increase response rates in the clinic.

Original languageEnglish (US)
Pages (from-to)891-896
Number of pages6
JournalInternational Journal of Cancer
Volume73
Issue number6
StatePublished - Dec 10 1997
Externally publishedYes

Fingerprint

irinotecan
Sarcoma
Ovarian Neoplasms
Neoplasms
Appointments and Schedules
Heterografts
Camptothecin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Jansen, W. J. M., Kolfschoten, G. M., Erkelens, C. A. M., Van Ark-Otte, J., Pinedo, H. M., & Boven, E. (1997). Anti-tumor activity of CPT-11 in experimental human ovarian cancer and human soft-tissue sarcoma. International Journal of Cancer, 73(6), 891-896.

Anti-tumor activity of CPT-11 in experimental human ovarian cancer and human soft-tissue sarcoma. / Jansen, Willy J M; Kolfschoten, Geertruida M.; Erkelens, Caroline A M; Van Ark-Otte, Jannette; Pinedo, Herbert M.; Boven, Epie.

In: International Journal of Cancer, Vol. 73, No. 6, 10.12.1997, p. 891-896.

Research output: Contribution to journalArticle

Jansen, WJM, Kolfschoten, GM, Erkelens, CAM, Van Ark-Otte, J, Pinedo, HM & Boven, E 1997, 'Anti-tumor activity of CPT-11 in experimental human ovarian cancer and human soft-tissue sarcoma', International Journal of Cancer, vol. 73, no. 6, pp. 891-896.
Jansen WJM, Kolfschoten GM, Erkelens CAM, Van Ark-Otte J, Pinedo HM, Boven E. Anti-tumor activity of CPT-11 in experimental human ovarian cancer and human soft-tissue sarcoma. International Journal of Cancer. 1997 Dec 10;73(6):891-896.
Jansen, Willy J M ; Kolfschoten, Geertruida M. ; Erkelens, Caroline A M ; Van Ark-Otte, Jannette ; Pinedo, Herbert M. ; Boven, Epie. / Anti-tumor activity of CPT-11 in experimental human ovarian cancer and human soft-tissue sarcoma. In: International Journal of Cancer. 1997 ; Vol. 73, No. 6. pp. 891-896.
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